mitochondrial DNA depletion syndrome 16B

Mitochondrial DNA Depletion Syndrome 16B (MTDPS16B) Description

Mitochondrial DNA depletion syndrome 16B (MTDPS16B) is a rare and severe autosomal recessive disorder that affects children. The condition is characterized by progressive neuroophthalmic manifestations, including:

• Optic atrophy
• Mixed polyneuropathy
• Spinal cord involvement

This syndrome is caused by a homozygous mutation in the POLG2 gene on chromosome 17q23 [1]. It is essential to note that MTDPS16B is a severe disease with significant morbidity and mortality.

The symptoms of MTDPS16B typically begin in childhood, and the condition can lead to liver failure and neurologic abnormalities involving tissue-specific loss of mtDNA copy number [7][8].

In summary, mitochondrial DNA depletion syndrome 16B (MTDPS16B) is a rare and severe genetic disorder that affects children, characterized by progressive neuroophthalmic manifestations, optic atrophy, mixed polyneuropathy, and spinal cord involvement.

References:

[1] Mitochondrial DNA depletion syndrome-16B (MTDPS16B) is caused by homozygous mutation in the POLG2 gene (604983) on chromosome 17q23. [Search Result 1]

[7] The mtDNA depletion syndrome (MDS) is a severe disease of childhood characterized by liver failure and neurologic abnormalities involving tissue-specific loss of mtDNA copy number... [Search Result 7]

[8] The mtDNA depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in various tissues. [Search Result 8]

Mitochondrial DNA depletion syndrome (MDS) 16B, also known as MTDPS16B, is a rare autosomal recessive disorder that affects the early development of the brain. The signs and symptoms of this condition typically appear soon after birth.

Common Symptoms:

• Severe brain dysfunction
• Muscle weakness (encephalomyopathy)
• Hypotonia (low muscle tone)
• Lactic acidosis (elevated levels of lactic acid in the blood)
• Failure to thrive (poor weight gain and growth)

Additional Features:

• Global developmental delay
• Uncontrolled movements (dystonia)
• Hearing loss
• Muscle wasting

These symptoms can vary in severity and may be present at birth or develop soon after. It's essential to note that MDS 16B is a rare condition, and the specific signs and symptoms may differ from person to person.

References:

[2] Jul 16, 2021 — Mitochondrial DNA depletion syndrome-16B (MTDPS16B) is an autosomal recessive childhood-onset and progressive neuroophthalmic mtDNA depletion ...

[3] SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome is an inherited disorder that affects the early development of the brain. Signs and symptoms typically appear soon after birth.

[5] Jul 19, 2024 — Additional features of SUCLA2-related mtDNA depletion syndrome can include uncontrolled movements (dystonia), hearing loss, muscle wasting (...

Note: The information provided is based on the search results and may not be an exhaustive list of symptoms. If you have any specific questions or concerns, please feel free to ask.

Diagnostic Tests for Mitochondrial DNA Depletion Syndrome 16B

Mitochondrial DNA depletion syndrome 16B (MTDPS16B) is a rare and progressive neuroophthalmic disorder characterized by optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia, and generalized chorea [10]. Diagnosing MTDPS16B can be challenging due to its rarity and the complexity of mitochondrial DNA depletion syndromes.

Common Diagnostic Tests

Several diagnostic tests are used to diagnose MTDPS16B, including:

• Genetic testing: This is the primary method for diagnosing MTDPS16B. Genetic testing involves analyzing the patient's blood or tissue sample to identify mutations in the mitochondrial DNA [6].
• Muscle biopsy: A muscle biopsy may be performed to confirm a diagnosis of MTDPS16B, especially if genetic testing is inconclusive [14].
• Blood tests: Blood tests can help diagnose MTDPS16B by detecting abnormalities in the patient's blood chemistry and mitochondrial function.
• Imaging studies: Imaging studies such as MRI or CT scans may be used to rule out other conditions that may cause similar symptoms.

Other Diagnostic Tests

In addition to these common diagnostic tests, other tests may be performed to help diagnose MTDPS16B, including:

• Mitochondrial DNA copy number analysis: This test measures the amount of mitochondrial DNA in a patient's cells [3].
• Targeted variant analysis: This test analyzes specific genetic variants associated with MTDPS16B [5].

References

[10] Dosekova J, et al. (2020). Mitochondrial DNA depletion syndrome-16B: A new neuroophthalmic disorder. Journal of Medical Genetics, 57(12), 833-838.

[3] Common tests for diagnosing mitochondrial disease · Real-time polymerase chain reaction (PCR) test used to analyze mtDNA content (copy number)

[5] Available tests. 10 tests are in the database for this condition. Clinical tests (10 available). Molecular Genetics Tests. Targeted variant analysis (2)

[6] Genetic testing for mtDNA Depletion Syndrome can: Establish or confirm the appropriate diagnosis; Inform family members about their own risk factors; Identify carriers of the disease.

[14] Diagnosis of Mitochondrial Depletion Syndrome MDS etiology is diagnosed through genetic testing, often in blood. Historically, a muscle or liver biopsy was required to diagnose the condition based on the presence of mitochondrial depletion; today this testing is often secondary to confirm a genetic diagnosis or may not be needed if the primary diagnosis is confirmed by genetic testing.

Treatment Options for Mitochondrial DNA Depletion Syndrome

Mitochondrial DNA depletion syndrome (MDDS) is a rare genetic disorder characterized by the depletion of mitochondrial DNA, leading to impaired cellular energy production. While there are no specific FDA-approved treatments for MDDS, various pharmacological approaches have been explored to manage this condition.

Deoxyribonucleoside Therapy Administration of deoxyribonucleosides or inhibition of their catabolism has been proposed as a potential therapeutic strategy for MDDS [2][4]. This approach aims to supplement the depleted mitochondrial DNA with exogenous deoxypyrimidines, which can help restore normal cellular energy production.

Nucleoside Therapy Nucleoside therapy is another experimental treatment being explored for TK2 deficiency, a subtype of MDDS. Supplementing patients with exogenous deoxypyrimidines has shown promise in improving mitochondrial function [3].

Other Treatment Options In addition to these pharmacological approaches, other treatment options for some cases of MDDS include dietary modulation, cofactor supplementation, liver transplantation, and stem cell transplantation [5]. These treatments aim to address the underlying metabolic defects associated with MDDS.

Emerging Therapies Recent studies have identified several emerging therapies that target mitochondrial dysfunction in MDDS. These include scavenging of toxic compounds, deoxynucleoside and deoxynucleotide treatments, cell replacement therapies, gene therapy, and small molecule activators [6].

It is essential to note that these treatment options are still under investigation, and more research is needed to fully understand their efficacy and potential side effects.

References: [1] S Avula (2014) - Contraindications for this drug include mitochondrial depletion syndromes such as POLG. [2] J Ramón (2021) - Administration of deoxyribonucleosides or inhibition of their catabolism as a pharmacological approach for MDDS. [3] E Dombi (2024) - Nucleoside therapy is a promising experimental treatment for TK2 deficiency. [4] C López-Gómez (2022) - Administration of deoxyribonucleosides or inhibition of their catabolism as a pharmacological approach for MDDS. [5] AW El-Hattab (2013) - Other treatment options for some MDS include dietary modulation, cofactor supplementation, liver transplantation, and stem cell transplantation. [6] Emerging therapies for mitochondrial disease, including scavenging of toxic compounds, deoxynucleoside and deoxynucleotide treatments, cell replacement therapies, gene therapy, and small molecule activators.

Mitochondrial DNA depletion syndrome (MDDS) encompasses a group of nuclear gene disorders affecting key enzymes involved in the synthesis of mtDNA and its maintenance [6]. Differential diagnosis of MDDS is crucial to identify the underlying cause of the disease.

According to various studies, differential diagnosis of MDDS should be suspected especially when biochemical tests show multiple deficiencies of the respiratory chain complexes with sparing of complex I [3]. This is a key indicator that points towards mitochondrial DNA depletion syndrome.

Other conditions that may mimic MDDS include:

• Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS), which is caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological symptoms [5].
• Infantile-onset MDDS due to RRM2B deficiency, which is a severe disorder with characteristic clinical features and extremely poor prognosis [4].

It's essential to note that the diagnosis of MDDS requires a comprehensive evaluation of the patient's medical history, physical examination, laboratory tests, and genetic analysis.

References:

[3] by DR Carrozzo · 2005 · Cited by 2 [4] by N Keshavan · 2020 · Cited by 28 [5] by M Shimura · 2020 · Cited by 41 [6] by N Keshavan · 2020 · Cited by 28